Gallic acid has anticancer activity and enhances the anticancer effects of cisplatin in non‑small cell lung cancer A549 cells via the JAK/STAT3 signaling pathway

Zhang,Tingxiu; Ma,Lijie; Wu,Pengfei; Li,Wei; Li,Ting; Gu,Rui; Dan,Xiaoping; Li,Zhiwei; Fan,Xianming; Xiao,Zhenliang

doi:10.3892/or.2019.6976

Gallic acid has anticancer activity and enhances the anticancer effects of cisplatin in non‑small cell lung cancer A549 cells via the JAK/STAT3 signaling pathway

Authors:
- Tingxiu Zhang
- Lijie Ma
- Pengfei Wu
- Wei Li
- Ting Li
- Rui Gu
- Xiaoping Dan
- Zhiwei Li
- Xianming Fan
- Zhenliang Xiao
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Affiliations: Department of Respiratory Diseases, The General Hospital of Western Theater Command, Chengdu, Sichuan 610083, P.R. China, Department of Central Laboratory, The General Hospital of Western Theater Command, Chengdu, Sichuan 610083, P.R. China, Department of Respiratory Diseases, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
Published online on: January 22, 2019 https://doi.org/10.3892/or.2019.6976
Pages: 1779-1788

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Abstract

Gallic acid (3,4,5‑trihydroxybenzoic acid; GA), a plant‑derived natural phenolic compound, has been reported to prevent the development and progression of various types of cancers. However, there has been little elaboration of the anticancer effects and underlying mechanisms of GA alone and/or in combination with cisplatin in non‑small cell lung cancer (NSCLC). The aim of the present study was to investigate the anticancer effects of GA on NSCLC A549 cells and its auxiliary effects on the anticancer activity of cisplatin. The results revealed that GA inhibited the proliferation and induced the apoptosis of NSCLC A549 cells in dose‑ and time‑dependent manners, which was associated with upregulated B‑cell lymphoma 2 (Bcl‑2)‑associated X protein (Bax) and downregulated Bcl‑2. Notably, the results also indicated that GA enhanced the anticancer effects of cisplatin in the inhibition of cancer cell proliferation and the induction of cell apoptosis following elevated Bax expression and suppressed Bcl‑2 expression. Furthermore, the results of the present study also demonstrated that GA exerted independent anticancer effects on NSCLC A549 cells, and facilitated the anticancer effects of cisplatin by modulating the JAK/STAT3 signaling pathway and downstream apoptotic molecules. These results may serve as a rationale for further basic studies and preclinical investigations on the anticancer effects of GA and its auxiliary effects on cisplatin function in human NSCLC.

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1	Zhu F, Dai C, Fu Y, Loo JF, Xia D, Gao SP, Ma Z and Chen Z: Physalin A exerts antitumor activity in non-small cell lung cancer cell lines by suppressing JAK/STAT3 signaling. Oncotarget. 7:9462–9476. 2016.PubMed/NCBI
2	Kubo H, Suzuki T, Matsushima T, Ishihara H, Uchino K, Suzuki S, Tada S, Yoshimura M and Kondo T: Cyclin-dependent kinase-specific activity predicts the prognosis of stage I and stage II non-small cell lung cancer. Bmc Cancer. 14:7552014. View Article : Google Scholar : PubMed/NCBI
3	Cromie MM and Gao W: Epigallocatechin-3-gallate enhances the therapeutic effects of leptomycin B on human lung cancer a549 cells. Oxid Med Cell Longev 2015. 2173042015.
4	Zheng XJ, Yang ZX, Dong YJ, Zhang GY, Sun MF, An XK, Pan LH and Zhang SL: Downregulation of leptin inhibits growth and induces apoptosis of lung cancer cells via the Notch and JAK/STAT3 signaling pathways. Biol Open. 5:794–800. 2016. View Article : Google Scholar : PubMed/NCBI
5	Carbone DP, Gandara DR, Antonia SJ, Zielinski C and Paz-Ares L: Non-small-cell lung cancer: Role of the immune system and potential for immunotherapy. J Thorac Oncol. 10:974–984. 2015. View Article : Google Scholar : PubMed/NCBI
6	Chang YJ, Hsu SL, Liu YT, Lin YH, Lin MH, Huang SJ, Ho JA and Wu LC: Gallic acid induces necroptosis via TNF-α signaling pathway in activated hepatic stellate cells. PLoS One. 10:e1207132015.
7	Wang R, Ma L, Weng D, Yao J, Liu X and Jin F: Gallic acid induces apoptosis and enhances the anticancer effects of cisplatin in human small cell lung cancer H446 cell line via the ROS-dependent mitochondrial apoptotic pathway. Oncol Rep. 35:3075–3083. 2016. View Article : Google Scholar : PubMed/NCBI
8	Kaur M, Velmurugan B, Rajamanickam S, Agarwal R and Agarwal C: Gallic acid, an active constituent of grape seed extract, exhibits anti-proliferative, pro-apoptotic and antitumorigenic effects against prostate carcinoma xenograft growth in nude mice. Pharm Res. 26:2133–2140. 2009. View Article : Google Scholar : PubMed/NCBI
9	He Z, Chen AY, Rojanasakul Y, Rankin GO and Chen YC: Gallic acid, a phenolic compound, exerts anti-angiogenic effects via the PTEN/AKT/HIF-1alpha/VEGF signaling pathway in ovarian cancer cells. Oncol Rep. 35:291–297. 2016. View Article : Google Scholar : PubMed/NCBI
10	Lee JH, Kim C, Baek SH, Ko JH, Lee SG, Yang WM, Um JY, Sethi G and Ahn KS: Capsazepine inhibits JAK/STAT3 signaling, tumor growth, and cell survival in prostate cancer. Oncotarget. 8:17700–17711. 2017.PubMed/NCBI
11	Wen W, Liang W, Wu J, Kowolik CM, Buettner R, Scuto A, Hsieh MY, Hong H, Brown CE, Forman SJ, et al: Targeting JAK1/STAT3 signaling suppresses tumor progression and metastasis in a peritoneal model of human ovarian cancer. Mol Cancer Ther. 13:3037–3048. 2014. View Article : Google Scholar : PubMed/NCBI
12	Zhou F, Cheng L, Qiu LX, Wang MY, Li J, Sun MH, Yang YJ, Wang JC, Jin L, Wang YN and Wei QY: Associations of potentially functional variants in IL-6, JAKs, STAT3 with gastric cancer risk in an eastern Chinese population. Oncotarget. 7:28112–28123. 2016.PubMed/NCBI
13	Gritsina G, Xiao F, O'Brien SW, Gabbasov R, Maglaty MA, Xu RH, Thapa RJ, Zhou Y, Nicolas E, Litwin S, et al: Targeted blockade of JAK/STAT3 signaling inhibits ovarian carcinoma growth. Mol Cancer Ther. 14:1035–1047. 2015. View Article : Google Scholar : PubMed/NCBI
14	Yang CL, Liu YY, Ma YG, Xue YX, Liu DG, Ren Y, Liu XB, Li Y and Li Z: Curcumin blocks small cell lung cancer cells migration, invasion, angiogenesis, cell cycle and neoplasia through Janus kinase-STAT3 signalling pathway. PLoS One. 7:e379602012. View Article : Google Scholar : PubMed/NCBI
15	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
16	Lee CY, Sher HF, Chen HW, Liu CC, Chen CH, Lin CS, Yang PC, Tsay HS and Chen JJ: Anticancer effects of tanshinone I in human non-small cell lung cancer. Mol Cancer Ther. 7:3527–3538. 2008. View Article : Google Scholar : PubMed/NCBI
17	Yu J, Xiao J, Yang Y and Cao B: Oxaliplatin-based doublets versus cisplatin or carboplatin-based doublets in the first-line treatment of advanced nonsmall cell lung cancer. Medicine. 94:e10722015. View Article : Google Scholar : PubMed/NCBI
18	Qian HR, Shi ZQ, Zhu HP, Gu LH, Wang XF and Yang Y: Interplay between apoptosis and autophagy in colorectal cancer. Oncotarget. 8:62759–62768. 2017. View Article : Google Scholar : PubMed/NCBI
19	Liu G, Pei F, Yang F, Li L, Amin AD, Liu S, Buchan JR and Cho WC: Role of autophagy and apoptosis in non-small-cell lung cancer. Int J Mol Sci. 18(pii): E3672017. View Article : Google Scholar : PubMed/NCBI
20	Jin G, Zhao J, Yang YI, Liu K, Jiang Y, Zhang X, Zhang Y, Huang Y, Lu J and Dong Z: JAK/STAT3 signaling pathway mediates endothelial-like differentiation of immature dendritic cells. Oncol Lett. 10:3471–3477. 2015. View Article : Google Scholar : PubMed/NCBI
21	Fang J, Lau V, Wu PC, Lai CL and Lau J: Imbalance between cell proliferation and programmed cell dealth apoptosis in hepatocellular carcinoma. Gastroenterology. 108 (4 Suppl 3):A10631995. View Article : Google Scholar
22	Wei W, Wu J, Liu L, Tian Y, Buettner R, Hsieh MY, Horne H, Dellinger TH, Han ES, Jove R, et al: Synergistic antitumor effect of combined inhibition of EGFR and JAK/STAT3 pathways in human ovarian cancer. Mol Cancer. 14:1002015. View Article : Google Scholar : PubMed/NCBI
23	Tang SN, Fu J, Shankar S and Srivastava RK: EGCG enhances the therapeutic potential of gemcitabine and CP690550 by inhibiting STAT3 signaling pathway in human pancreatic cancer. PLoS One. 7:e310672012. View Article : Google Scholar : PubMed/NCBI
24	Wen W, Wu J, Liu L, Tian Y, Buettner R, Hsieh MY, Horne D, Dellinger TH, Han ES, Jove R, et al: Synergistic anti-tumor effect of combined inhibition of EGFR and JAK/STAT3 pathways in human ovarian cancer. Mol Cancer. 14:1002015. View Article : Google Scholar : PubMed/NCBI
25	Li S, Priceman SJ, Xin H, Zhang W, Deng J, Liu Y, Huang J, Zhu W, Chen M, Hu W, et al: Icaritin inhibits JAK/STAT3 signaling and growth of renal cell carcinoma. PLoS One. 8:e816572013. View Article : Google Scholar : PubMed/NCBI